曲古抑菌素A对胃癌细胞生长的抑制作用  

Trichostatin A inhibits the growth of human gastric cancer SGC-7901 cells

作　　者：乔文[1] 杨晓丹[1] 王丹[1] 

机构地区：[1]西安交通大学医学院第一附属医院消化科,陕西省西安市710061

出　　处：《世界华人消化杂志》2009年第35期3611-3614,共4页World Chinese Journal of Digestology

摘　　要：目的:研究组蛋白去乙酰化酶抑制剂-曲古抑菌素A(trichostatin A,TSA)对胃癌细胞系SGC-7901的生长抑制作用,证实该作用是通过促使细胞凋亡而实现的.方法:用不同浓度(0.2、0.4和0.8mg/L)和不同作用时间(24、48和72h)的TSA作用于SGC-7901细胞,采用MTT法观察TSA对SGC-7901细胞增殖的抑制作用;通过流式细胞仪检测细胞周期和凋亡率的变化;通过透射电镜观察细胞超微结构的变化.结果:TSA可抑制胃癌SGC-7901细胞的生长,且这种作用呈时间和剂量依赖关系.当TSA作用浓度分别为0.2、0.4和0.8mg/L时,与SGC-7901细胞均作用72h,TSA对SGC-7901细胞生长的抑制率分别为25%±1.2%,45%±1.4%和73%±1.7%,各组均与TSA0.2mg/L组比较,差异显著(P<0.05).当0.8mg/LTSA分别与SGC-7901细胞作用24、48和72h,TSA对SGC-7901细胞生长的抑制率分别为21%±1.1%,37%±2.0%和73%±1.7%,各组均与TSA作用24h组比较,差异显著(P<0.05).TSA可延缓细胞周期,具有明显的诱导细胞凋亡作用.电镜下见细胞染色质凝聚成段片状,细胞核固缩断裂,核膜破裂,细胞器及胞膜自溶,凋亡小体形成.结论:TSA通过诱导细胞周期阻止和凋亡来抑制胃癌细胞系SGC-7901的生长,且这种作用呈时间和剂量依赖性,为TSA用于胃癌的治疗提供理论依据.AIM： To investigate the inhibitory effects of trichostatin A （TSA） on the growth of human gastric cancer SGC-7901 cells and explore potential mechanisms involved. METHODS： SGC-7901 cells were treated with different concentrations （0.2, 0.4 and 0.8 mg/L） of TSA for different durations （24, 48 and 72 h）. Cell proliferation was detected by methyl thiazolyl tetrazolium （MTT） assay. Cell cycle distribution and apoptotic rate were detected by flow cytometry. Cell ultrastructure was observed using transmission electron microscopy （TEM）. RESULTS： SGC-7901 cells were very sensitive to TSA. TSA inhibited the growth of SGC-7901 cells in a concentration- and time-dependent manner. The reduced rates of growth in cells treated with TSA at concentrations of 0.4 and 0.8 mg/L for 72 h were significantly higher than that in cells treated with TSA at a concentration of 0.2 mg/L for the same duration （45% ± 1.4% and 73% ±1.7% vs 25% ±1.2%, respectively; both P 〈 0.05）. The reduced rates of growth in cell treated with TSA at concentrations of 0.8 mg/L for 48 and 72 h were significantly higher than that in cells treated with TSA at the same concentration for 24 hours （37% ± 2.0% and 73% ± 1.7% vs 21% ± 1.1%, respectively; both P 〈 0.05）. TSA could induce apoptosis of SGC-7901 cells. The ultrastructure changes in SGC-7901 cells treated with TSA included nuclear fragmentation, nuclear membrane rupture, membrane and organelle dissolution, and formation of vacuoles and apoptotic bodies. CONCLUSION： TSA can inhibit cell growth and induce apoptosis in human gastric cancer cell line SGC-7901 in a concentration- and timedependent manner.

关 键 词：曲古抑菌素A 胃癌SGC-7901细胞 细胞周期 凋亡 

分 类 号：R735.2[医药卫生—肿瘤]